We intend to derive monoclonal antibodies and to derive clones of murine T cells which recognize sperm whale myoglobin. Using cleavage fragments of myoglobin we will select T cell clones which look at restricted or isolated epitopes contained in the native molecule and compare the epitope recognized by helper and/or suppressor T cells to that recognized by immunoglobulin molecules. Using such epitopes we will be able to study in depth mechanisms of MHC restriction and antigen presentation which result in immune response phenomena. By raising anti-idiotypic antibodies against conventional antibodies to myoglobin which have been affinity purified on cleavage fragments of myoglobin, we will be able to question whether or not T helper cell clones or T suppressor cell clones that react with the same cleavage fragment share idiotype with immunoglobulin molecules recognizing that same fragment. Additionally, by raising murine T cell clones reactive with idiotypic determinants on monoclonal antibodies exhibiting specificity toward well defined epitopes on myoglobin, we should be able to look at help provided by such anti-idiotypic T cell clones and their possible interactions with idiotype bearing T cell clones. These studies will allow us to explore the implications concerning regulation by anti-idiotypic T help or suppression implicit in the Jerne network theory. These studies are directed at analyzing problems which are basic to the understanding of immunocompetent cellular interactions and communication. We will pursue the studies outlined above using the technology of monoclonal antibody production and isolation of T cell clones which are currently available in my laboratory. We have preliminary studies which show that it will be possible to isolate clones of T cells reactive with individual epitopes on myoglobin, as well as to generate monoclonal antibodies recognizing epitopes on the same cleavage fragment. Biochemical characterization of products of such cloned antigen-reactive T cells, as well as biochemical isolation and characterization of antigen sites recognized by such cloned T cells and monoclonal antibodies will be performed as outlined in the body of this grant proposal utilizing conventional technology.